Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD
We performed a panoramic analysis on both human nonalcoholic steatohepatitis (NASH) microarray data and microarray/RNA-seq data from various mouse models of nonalcoholic fatty liver disease NASH/NAFLD with total 4249 genes examined and made the following findings: (i) human NASH and NAFLD mouse mode...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/3928323 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832564807844233216 |
|---|---|
| author | Charles I. V. Drummer Fatma Saaoud Yu Sun Diana Atar Keman Xu Yifan Lu Ying Shao Candice Johnson Lu Liu Huimin Shen Nirag C. Jhala Xiaohua Jiang Hong Wang Xiaofeng Yang |
| author_facet | Charles I. V. Drummer Fatma Saaoud Yu Sun Diana Atar Keman Xu Yifan Lu Ying Shao Candice Johnson Lu Liu Huimin Shen Nirag C. Jhala Xiaohua Jiang Hong Wang Xiaofeng Yang |
| author_sort | Charles I. V. Drummer |
| collection | DOAJ |
| description | We performed a panoramic analysis on both human nonalcoholic steatohepatitis (NASH) microarray data and microarray/RNA-seq data from various mouse models of nonalcoholic fatty liver disease NASH/NAFLD with total 4249 genes examined and made the following findings: (i) human NASH and NAFLD mouse models upregulate both cytokines and chemokines; (ii) pathway analysis indicated that human NASH can be classified into metabolic and immune NASH; methionine- and choline-deficient (MCD)+high-fat diet (HFD), glycine N-methyltransferase deficient (GNMT-KO), methionine adenosyltransferase 1A deficient (MAT1A-KO), and HFCD (high-fat-cholesterol diet) can be classified into inflammatory, SAM accumulation, cholesterol/mevalonate, and LXR/RXR-fatty acid β-oxidation NAFLD, respectively; (iii) canonical and noncanonical inflammasomes play differential roles in the pathogenesis of NASH/NAFLD; (iv) trained immunity (TI) enzymes are significantly upregulated in NASH/NAFLD; HFCD upregulates TI enzymes more than cytokines, chemokines, and inflammasome regulators; (v) the MCD+HFD is a model with the upregulation of proinflammatory cytokines and canonical and noncanonical inflammasomes; however, the HFCD is a model with upregulation of TI enzymes and lipid peroxidation enzymes; and (vi) caspase-11 and caspase-1 act as upstream master regulators, which partially upregulate the expressions of cytokines, chemokines, canonical and noncanonical inflammasome pathway regulators, TI enzymes, and lipid peroxidation enzymes. Our findings provide novel insights on the synergies between hyperlipidemia and hypomethylation in establishing TI and promoting inflammation in NASH and NAFLD progression and novel targets for future therapeutic interventions for NASH and NAFLD, metabolic diseases, transplantation, and cancers. |
| format | Article |
| id | doaj-art-1fd1eeed479244ef8554a63a366e4bd8 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1fd1eeed479244ef8554a63a366e4bd82025-02-03T01:10:08ZengWileyJournal of Immunology Research2314-71562021-01-01202110.1155/2021/3928323Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLDCharles I. V. Drummer0Fatma Saaoud1Yu Sun2Diana Atar3Keman Xu4Yifan Lu5Ying Shao6Candice Johnson7Lu Liu8Huimin Shen9Nirag C. Jhala10Xiaohua Jiang11Hong Wang12Xiaofeng Yang13Centers for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationCenters for Cardiovascular Research and InflammationMetabolic Disease Research and Thrombosis ResearchMetabolic Disease Research and Thrombosis ResearchDepartment of PathologyCenters for Cardiovascular Research and InflammationMetabolic Disease Research and Thrombosis ResearchCenters for Cardiovascular Research and InflammationWe performed a panoramic analysis on both human nonalcoholic steatohepatitis (NASH) microarray data and microarray/RNA-seq data from various mouse models of nonalcoholic fatty liver disease NASH/NAFLD with total 4249 genes examined and made the following findings: (i) human NASH and NAFLD mouse models upregulate both cytokines and chemokines; (ii) pathway analysis indicated that human NASH can be classified into metabolic and immune NASH; methionine- and choline-deficient (MCD)+high-fat diet (HFD), glycine N-methyltransferase deficient (GNMT-KO), methionine adenosyltransferase 1A deficient (MAT1A-KO), and HFCD (high-fat-cholesterol diet) can be classified into inflammatory, SAM accumulation, cholesterol/mevalonate, and LXR/RXR-fatty acid β-oxidation NAFLD, respectively; (iii) canonical and noncanonical inflammasomes play differential roles in the pathogenesis of NASH/NAFLD; (iv) trained immunity (TI) enzymes are significantly upregulated in NASH/NAFLD; HFCD upregulates TI enzymes more than cytokines, chemokines, and inflammasome regulators; (v) the MCD+HFD is a model with the upregulation of proinflammatory cytokines and canonical and noncanonical inflammasomes; however, the HFCD is a model with upregulation of TI enzymes and lipid peroxidation enzymes; and (vi) caspase-11 and caspase-1 act as upstream master regulators, which partially upregulate the expressions of cytokines, chemokines, canonical and noncanonical inflammasome pathway regulators, TI enzymes, and lipid peroxidation enzymes. Our findings provide novel insights on the synergies between hyperlipidemia and hypomethylation in establishing TI and promoting inflammation in NASH and NAFLD progression and novel targets for future therapeutic interventions for NASH and NAFLD, metabolic diseases, transplantation, and cancers.http://dx.doi.org/10.1155/2021/3928323 |
| spellingShingle | Charles I. V. Drummer Fatma Saaoud Yu Sun Diana Atar Keman Xu Yifan Lu Ying Shao Candice Johnson Lu Liu Huimin Shen Nirag C. Jhala Xiaohua Jiang Hong Wang Xiaofeng Yang Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD Journal of Immunology Research |
| title | Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD |
| title_full | Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD |
| title_fullStr | Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD |
| title_full_unstemmed | Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD |
| title_short | Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD |
| title_sort | hyperlipidemia may synergize with hypomethylation in establishing trained immunity and promoting inflammation in nash and nafld |
| url | http://dx.doi.org/10.1155/2021/3928323 |
| work_keys_str_mv | AT charlesivdrummer hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT fatmasaaoud hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT yusun hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT dianaatar hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT kemanxu hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT yifanlu hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT yingshao hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT candicejohnson hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT luliu hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT huiminshen hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT niragcjhala hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT xiaohuajiang hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT hongwang hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld AT xiaofengyang hyperlipidemiamaysynergizewithhypomethylationinestablishingtrainedimmunityandpromotinginflammationinnashandnafld |